The understanding of skin lymphomas has followed the evolution of lymph node
based lymphomas. There has been an explosive growth in the classification
of these lymphomas with new insights gained from molecular biology, hematopathology,
and immunohistochemistry. Ultimately, the utility of any classification system
is to predict behavior of each cancer and help to direct therapy. The EORTC
classification is one system that does a fine job of organizing the myriad
of names of cutaneous lymphomas. Briefly, cutaneous lymphomas can be divided
into T and B cell lineage, with T cell lymphomas the most common. Within these
divisions, further distinctions based upon the clinical behavior can be gleaned.

It must be remembered that cutaneous lymphomas are relatively rare. Of these
variants, mycosis fungoides is the most
common and sometimes has been used indiscriminately to describe all cutaneous
T cell lymphomas (CTCL). To further complicate matters, there are a few skin
rashes which have been classified under CTCL which at best, have an unpredictable
behavior with an increased risk of progression to lymphoma. These rashes called
parapsoriasis have been broadly divided into small and large plaque
parapsoriasis. The name derives from the clinical appearance of these scaly
rashes which resemble psoriasis. These rashes were chronic conditions and
relatively resistant to therapy. Within recent years, large plaque parapsoriasis
(also known as atrophic parapsoriasis, retiform parapsoriasis, and poikilodermal
atrophicans vasculare) has become synonymous with mycosis fungoides. Careful
studies have found progression to CTCL in 10-30% of cases. The problem is
identifying which cases will progress. The lesions usually start as large
erythematous patch or plaque on the trunk or extremities, usually 10 cm. or
more in diameter. Atrophy may follow and nearly all cases which have progressed
to lymphoma have done so through this atrophic stage.

Finally, there are a number of skin diseases which have been broadly classified
as pseudolymphomas. These entities mimic
cutaneous lymphomas both clinically and histologically but are benign.

The pathogenesis or origin of cutaneous lymphomas is actively debated. One
theory suggests an early precursor lesion with a persistent stimulation by
an antigen, possibly a superantigen. This leads to epidermal derived growth
factors which attract lymphocytes. Additional acquired defects in cell cycle
regulation and apoptosis, early CTCL may develop. These neoplastic T-helper-2
cells proliferate because they cannot be blocked by endogenous interferon-gamma
because of IFN-gamma resistance. There is a low proliferation rate at this
point. With increasing genetic alterations, there is a reduced dependency
on epidermal derived growth factors and subsequently a high proliferation
rate.

In contrast, cutaneous B cell lymphomas (CBCL) have
a different pathogenesis. Like CTCL, they are antigen driven processes. It
appears that heavy chain genes (VH) of the B cells show significant mutations.
Once this occurs, a neoplastic clone develops. There are definitely some environmental
factors associated with this such as Borrelia burgdorferi infection (agent
of Lyme disease). The term SALT (Skin Associated Lymphoid Tissue) has
been applied to some of these B cell lymphomas, citing the similarity of CBCL
with other B cell lymphomas arising within mucosa such as the salivary gland
and gastrointestinal tract.

We determined the frequency of the V beta in normal and inflamed skin
and compared it to the percentage of the respective V beta in the malignant
clone of the CTCL patients. The percentage of the V beta positive CD4+
cells in relation to the total number of T cells in normal skin and
inflamed skin differed from the distribution of the V beta families
in the peripheral blood mononuclear cells (PBMC). Out of 71 CTCL cases,
the clone was identified in 23 (32%).

In 6 patients, the malignant clone was mainly localized in the epidermis.
In 17 cases, the clone-specific cells were distributed in epidermis
and dermis equally. A retrospective analysis showed that preferential
epidermal homing of the clone was associated with a non-aggressive clinical
course. The V beta usage of CTCL and eczema suggests a special cutaneous
microenvironment which might be co-created by certain (bacterial?) superantigens.
A preferential epidermal homing of the clone might have prognostic implications.

Department of Dermatology, University of Texas Medical School, Houston,
USA.

Blood 1997 Jan 1;89(1):32-40 Abstract quote

Forty-two patients with cutaneous T-cell lymphoma, including 31 with
exfoliative erythroderma or Sezary syndrome and 11 with mycosis fungoides,
were studied for the occurrence of staphylococcal infection.

Thirty-two of 42 (76%) had a positive staphylococcal culture from skin
or blood. One half of the patients with positive cultures grew Staphylococcus
aureus. This group included 11 with Sezary syndrome and 5 with rapidly
enlarging mycosis fungoides plaques or tumors. All of the S aureus carried
enterotoxin genes. Surprisingly, 6 of 16 strains were the same toxic
shock toxin-1 (TSST-1)-positive clone, designated electrophoretic type
(ET)-41. Analysis of the T-cell receptor V beta repertoire in 14 CTCL
patients found that only 4 had the expected monoclonal expansion of
a specific V beta gene, whereas 10 had oligoclonal or polyclonal expansion
of several V beta families. All patients with TSST-1+ S aureus had overexpansion
of V beta Z in blood and/or skin lesions.

These studies show that S aureus containing superantigen enterotoxins
are commonly found in patients with CTCL especially individuals with
erythroderma where they could exacerbate and/or perpetuate stimulate
chronic T-cell expansion and cutaneous inflammation. Attention to toxigenic
S aureus in CTCL patients would be expected to improve the quality of
care and outcome of this patient population.

Accurate evaluation of patients with suspected or known cutaneous lymphoma
requires the integration of many sources and types of information, including
clinical evaluation, microscopic analysis of tissue, immunophenotyping,
gene rearrangement studies, clinical staging, and longitudinal observation.
Diagnoses should be based on knowledge of specific lymphoma types as
described in modern classification systems.

There were seven women and eight men with a mean age at diagnosis of
53 years (range 1977 years). All but two patients presented with
solitary or multiple cutaneous nodule(s). Initial and recurrent biopsy
specimens showed a dense infiltrate centered in the mid-dermis (extending
into subcutis when sampled) of small to intermediate-sized lymphocytes
with indistinct nucleoli and frequently irregular nuclear contours.
Periadnexal infiltration and epidermal ulceration were present in five
cases with the intraepidermal cells being primarily reactive CD4+ T
cells. All cases were negative for CD30 and terminal deoxynucleotidyltransferase;
one showed expression of CD56, and six of eight tested cases were positive
for T-cell receptor- expression.

Objective
To evaluate the clinical and prognostic features in primary cutaneous
CD8+ T-cell lymphomas, which are rare and considered to be aggressive
cutaneous lymphoproliferative disorders.

Design
Single-center retrospective study.

Setting
Lymphoma clinic (referral center) of a university hospital.

Patients
Three patients presented with CD8+ cutaneous lymphoma characterized
by a patchlike pattern and hyperpigmentation.

Results
Histological analysis revealed a CD3+, CD8+ small-cell infiltrate showing
a remarkable affinity to the dermoepidermal junction zone. Clonality
for the T-cell receptor chain was detected by polymerase chain reaction
followed by denaturing gradient gel electrophoresis. The clinical presentation
lasted several years (6 and 9 years, respectively) before the correct
diagnosis was made. Treatment with nontoxic approaches (UV-B and local
steroids) was successful. Aggressive clinical behavior was not observed.

Conclusions
Our 3 cases of junctional CD8+ cutaneous T-cell lymphomas were characterized
by hyperpigmentation and nonaggressive clinical behavior. This type
of lymphoma, which can be considered a CD8+ mycosis fungoides variant,
must be distinguished from other types of cutaneous CD8+ lymphomas so
that overtreatment can be avoided.

PLEOMORPHIC TYPE

Localized cutaneous small to medium-sized pleomorphic T-cell lymphoma:
A report of 3 cases stable for years.

von Den Driesch P, Coors EA.

Department of Dermatology, University of Erlangen-Nuremberg.

J Am Acad Dermatol 2002 Apr;46(4):531-5 Abstract quote

Small to medium-sized pleomorphic cutaneous T-cell lymphomas represent
a provisional entity in the new European Organization for Research and
Treatment of Cancer classification.

We describe 3 patients with a localized and outstanding stable variant
of this tumor. A median follow-up period of 50 months did not reveal
any spread into regional lymph nodes or to distant sites in any patient.

Weedon D. Weedon's Skin Pathology. Churchill Livingstone.
1997.

Commonly Used Terms

SALT-Skin-associated lymphoid tissue. Broad term used to describe
native B lymphocytes within the skin. It is theorized that these lymphocytes
may give rise to some CBCLs.